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1.
BMC Public Health ; 24(1): 2371, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223569

RESUMEN

BACKGROUND: Both body mass index (BMI) and genetic factors independently contribute to cardiovascular disease (CVD). However, it is unclear whether genetic risk modifies the association between BMI and the risk of incident CVD. This study aimed to investigate whether BMI categories and genetic risk jointly and interactively contribute to incident CVD events, including hypertension (HTN), atrial fibrillation (AF), coronary heart disease (CHD), stroke, and heart failure (HF). METHODS: A total of 496,851 participants from the UK Biobank with one or more new-onset CVD events were included in the analyses. BMI was categorized as normal weight (< 25.0 kg/m2), overweight (25.0-29.9 kg/m2), and obesity (≥ 30.0 kg/m2). Genetic risk for each outcome was defined as low (lowest tertile), intermediate (second tertile), and high (highest tertile) using polygenic risk score. The joint associations of BMI categories and genetic risk with incident CVD were investigated using Cox proportional hazard models. Additionally, additive interactions were evaluated. RESULTS: Among the 496,851 participants, 270,726 (54.5%) were female, with a mean (SD) age was 56.5 (8.1) years. Over a median follow-up (IQR) of 12.4 (11.5-13.1) years, 102,131 (22.9%) participants developed HTN, 26,301 (5.4%) developed AF, 32,222 (6.9%) developed CHD, 10,684 (2.2%) developed stroke, and 13,304 (2.7%) developed HF. Compared with the normal weight with low genetic risk, the obesity with high genetic risk had the highest risk of CVD: HTN (HR: 3.96; 95%CI: 3.84-4.09), AF (HR: 3.60; 95%CI: 3.38-3.83), CHD (HR: 2.76; 95%CI: 2.61-2.91), stroke (HR: 1.44; 95%CI: 1.31-1.57), and HF (HR: 2.47; 95%CI: 2.27-2.69). There were significant additive interactions between BMI categories and genetic risk for HTN, AF, and CHD, with relative excess risk of 0.53 (95%CI: 0.43-0.62), 0.67 (95%CI: 0.51-0.83), and 0.37 (95%CI: 0.25-0.49), respectively. CONCLUSIONS: BMI and genetic factors jointly and interactively contribute to incident CVD, especially among participants with high genetic risk. These findings have public health implications for identifying populations more likely to have cardiovascular benefit from weight loss interventions.


Asunto(s)
Bancos de Muestras Biológicas , Índice de Masa Corporal , Enfermedades Cardiovasculares , Humanos , Femenino , Masculino , Reino Unido/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Anciano , Predisposición Genética a la Enfermedad , Adulto , Factores de Riesgo , Obesidad/epidemiología , Obesidad/genética , Incidencia , Biobanco del Reino Unido
2.
BMC Public Health ; 24(1): 2354, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39210312

RESUMEN

BACKGROUND: Both ambient air pollution and lifestyle factors contribute to the incidence of non-alcoholic fatty liver disease (NAFLD), but previous studies usually focused on single-factor associations. We aimed to assess the joint associations of ambient air pollution and lifestyle with the NAFLD risk and investigate whether lifestyle modifies the association of air pollution with NAFLD risk. METHODS: A total of 417,025 participants from the UK Biobank were included in this study. Annual average concentrations of NO2, NOx, PM2.5, PM10, and PM2.5-10 were estimated. A composite lifestyle score was determined based on physical activity, alcohol intake, smoking status, dietary patterns, sedentary time, and sleep duration. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs), as well as the population attributable fraction (PAF). Potential additive interactions of air pollution with lifestyle were also examined by the relative excess risk due to the interaction (RERI) and the attributable proportion due to the interaction (AP). RESULTS: 4752 (1.14%) incident NAFLD events were recorded. Long-term exposure to air pollutants and an unhealthy lifestyle were significantly associated with the increased risk of incident NAFLD. Lifestyle was the primary factor of incident NAFLD, with a PAF of 37.18% (95% CI: 29.67%, 44.69%). In addition, a significant additive interaction between air pollution and lifestyle for NAFLD risk was observed (RERI: 0.36, 95% CI: 0.09-0.63). CONCLUSIONS: Long-term exposure to ambient air pollutants and poor lifestyle were jointly associated with a higher risk of NAFLD.


Asunto(s)
Contaminación del Aire , Estilo de Vida , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/etiología , Femenino , Masculino , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Persona de Mediana Edad , Adulto , Reino Unido/epidemiología , Estudios de Cohortes , Factores de Riesgo , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Anciano , Incidencia , Exposición a Riesgos Ambientales/efectos adversos , Modelos de Riesgos Proporcionales
3.
Biom J ; 66(3): e2300094, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38581099

RESUMEN

Conditional power (CP) serves as a widely utilized approach for futility monitoring in group sequential designs. However, adopting the CP methods may lead to inadequate control of the type II error rate at the desired level. In this study, we introduce a flexible beta spending function tailored to regulate the type II error rate while employing CP based on a predetermined standardized effect size for futility monitoring (a so-called CP-beta spending function). This function delineates the expenditure of type II error rate across the entirety of the trial. Unlike other existing beta spending functions, the CP-beta spending function seamlessly incorporates beta spending concept into the CP framework, facilitating precise stagewise control of the type II error rate during futility monitoring. In addition, the stopping boundaries derived from the CP-beta spending function can be calculated via integration akin to other traditional beta spending function methods. Furthermore, the proposed CP-beta spending function accommodates various thresholds on the CP-scale at different stages of the trial, ensuring its adaptability across different information time scenarios. These attributes render the CP-beta spending function competitive among other forms of beta spending functions, making it applicable to any trials in group sequential designs with straightforward implementation. Both simulation study and example from an acute ischemic stroke trial demonstrate that the proposed method accurately captures expected power, even when the initially determined sample size does not consider futility stopping, and exhibits a good performance in maintaining overall type I error rates for evident futility.


Asunto(s)
Accidente Cerebrovascular Isquémico , Proyectos de Investigación , Humanos , Tamaño de la Muestra , Simulación por Computador , Inutilidad Médica
4.
J Biopharm Stat ; 33(1): 15-30, 2023 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-35791856

RESUMEN

Non-inferiority (NI) clinical trials are widely used to evaluate whether the new experimental treatment is not unacceptably worse than the current active-control treatment by more than a pre-specified non-inferiority margin (NI margin). However, choosing either an absolute difference [risk difference (RD)] or a relative difference [relative risk (RR) and odds ratio (OR)] to evaluate efficacy in NI clinical trials is still controversial. In this study, we aim to evaluate the performance of abovementioned three metrics for testing NI clinical trials with risk rate endpoint. Herein, extensive Monte Carlo simulations based on various parameter settings (NI margin as well as risk rates in the experimental group and active-control group) are conducted to compare the Type I error rate, statistical power, and the necessary sample size to achieve a desired power for testing NI using RD, RR, and OR. We show that testing NI using RD not only controls well the Type I error and achieves the highest statistical power but also requires the smallest sample size compared to RR and OR. In practice, however, the choice among three metrics still needs to be based upon clinical interpretations and regulatory perspectives.


Asunto(s)
Proyectos de Investigación , Humanos , Grupos Control , Oportunidad Relativa , Riesgo , Tamaño de la Muestra , Estudios de Equivalencia como Asunto
5.
Int J Mol Sci ; 24(2)2023 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-36675190

RESUMEN

Endometrial cancer has the highest incidence of uterine corpus cancer, the sixth most typical cancer in women until 2020. High recurrence rate and frequent adverse events were reported in either standard chemotherapy or combined therapy. Hence, developing precise diagnostic and prognostic approaches for endometrial cancer was on demand. Four hypoxia-related genes were screened for the EC prognostic model by the univariate, LASSO, and multivariate Cox regression analysis from the TCGA dataset. QT-PCR and functional annotation analysis were performed. Associations between predicted risk and immunotherapy and chemotherapy responses were investigated by evaluating expressions of immune checkpoint inhibitors, infiltrated immune cells, m6a regulators, and drug sensitivity. The ROC curve and calibration plot indicated a fair predictability of our prognostic nomogram model. NR3C1 amplification, along with IL-6 and SRPX suppressions, were detected in tumor. High stromal score and enriched infiltrated aDCs and B cells in the high-risk group supported the hypothesis of immune-deserted tumor. Hypoxia-related molecular subtypes of EC were then identified via the gene signature. Cluster 2 patients showed a significant sensitivity to Vinblastine. In summary, our hypoxia signature model accurately predicted the survival outcome of EC patients and assessed translational and transcriptional dysregulations to explore targets for precise medical treatment.


Asunto(s)
Neoplasias Endometriales , Hipoxia , Femenino , Humanos , Neoplasias Endometriales/genética , Hipoxia/genética , Nomogramas , Pronóstico
6.
Biol Proced Online ; 24(1): 9, 2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35836132

RESUMEN

BACKGROUND: Long non-coding RNAs (lncRNA) have been implicated in a hand of studies that supported an involvement and co-operation in Uterine Corpus Endometrial Carcinoma (UCEC). Enhancer RNAs (eRNA), a functional subtype of lncRNA, have a key role throughout the genome to guide protein production, thus potentially associated with diseases. METHODS: In this study, we mainly applied the Cancer Genome Atlas (TCGA) dataset to systematically discover crucial eRNAs involving UCEC. For the key eRNAs in UCEC, we employed RT-qPCR to compare eRNA expression levels in tumor tissues and paired normal adjacent tissues from UCEC patients for validation. Furthermore, the relationships between the key eRNAs and immune activities were measured from several aspects, including the analysis for tumor microenvironment, immune infiltration cells, immune check point genes, tumor mutation burden, and microsatellite instability, as well as m6A related genes. Finally, the key eRNAs were verified by a comprehensive pan-cancer analysis. RESULTS: IGFBP7 Antisense RNA 1 (IGFBP7-AS1) was identified as the key eRNA for its expression patterns of low levels in tumor tissues and favorable prognostic value in UCEC correlated with its target gene IGFBP7. In RT-qPCR analysis, IGFBP7-AS1 and IGFBP7 had down-regulated expression in tumor tissues, which was consistent with previous analysis. Moreover, IGFBP7-AS1 was found closely related with immune response in relevant immune analyses. Besides, IGFBP7-AS1 and its target gene IGFBP7 correlated with a multi-omics pan-cancer analysis. CONCLUSIONS: Finally, we suggested that IGFBP7-AS1 played a key role in impacting on clinical outcomes of UCEC patients for its possible influence on immune activity.

7.
Br J Nutr ; 127(9): 1386-1394, 2022 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-34165051

RESUMEN

Dyslipidaemia, a significant risk factor of CVD, is threatening human health worldwide. PUFA are crucial long-chain fatty acids for TAG synthesis and removal, potentially decreasing dyslipidaemia risk. We examined dyslipidaemia prevalence among 15 244 adults aged ≥ 20 years from National Health and Nutrition Examination Survey 2009-2016. Dyslipidaemia was defined as total cholesterol ≥ 240 mg/dl, or HDL-cholesterol < 40 mg/dl/50 mg/dl for males/females, respectively, or LDL-cholesterol ≥ 160 mg/dl, or TAG ≥ 200 mg/dl, or taking lipid-modifying medications. We measured the daily PUFA intake using a 24-h dietary recall. Demographics, social economics, and lifestyle factors were collected using questionnaires/interviews. Additionally, we measured Se and Hg levels in the whole blood. Logistic regression models were used to examine the association between PUFA and dyslipidaemia. The unweighted and weighted dyslipidaemia prevalences were 72·4% and 71·0 %, respectively. When grouped into tertiles, PUFA intake above 19·524 g/d was associated with an independent 19 % decrease in dyslipidaemia risk (OR = 0·81 (95 % CI 0·71, 0·94)) compared with the lowest tertile (PUFA intake ≤ 12·349 g/d). A threshold inverse association was further determined by the restricted cubic spline analysis. When PUFA intake was increased to its turning point, that is, 19 g/d, the lower nadir risk for dyslipidaemia was obtained (OR = 0·72 (95 % CI 0·56, 0·89)). When the exposure was the sum of α-linolenic acid and octadecatetraenoic acid, the inverse linear association remained. Dietary PUFA intake is a beneficial factor for dyslipidaemia among American adults, independent of many potential confounders, including Hg and Se.


Asunto(s)
Dieta , Dislipidemias , Adulto , Humanos , Masculino , Femenino , Estados Unidos , Encuestas Nutricionales , Estudios Transversales , HDL-Colesterol
8.
J Appl Stat ; 51(4): 646-663, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38414801

RESUMEN

Progression-free survival (PFS) is an increasingly important surrogate endpoint in cancer clinical trials. However, the true time of progression is typically unknown if the evaluation of progression status is only scheduled at given surveillance intervals. In addition, comparison between treatment arms under different surveillance schema is not uncommon. Our aim is to explore whether the heterogeneity of the surveillance intervals may interfere with the validity of the conclusion of efficacy based on PFS, and the extent to which the variation would bias the results. We conduct comprehensive simulation studies to explore the aforementioned goals in a two-arm randomized control trial. We introduce three steps to simulate survival data with predefined surveillance intervals under different censoring rate considerations. We report the estimated hazard ratios and examine false positive rate, power and bias under different surveillance intervals, given different baseline median PFS, hazard ratio and censoring rate settings. Results show that larger heterogeneous lengths of surveillance intervals lead to higher false positive rate and overestimate the power, and the effect of the heterogeneous surveillance intervals may depend upon both the life expectancy of the tumor prognoses and the censoring proportion of the survival data. We also demonstrate such heterogeneity effect of surveillance intervals on PFS in a phase III metastatic colorectal cancer trial. In our opinions, adherence to consistent surveillance intervals should be favored in designing the comparative trials. Otherwise, it needs to be appropriately taken into account when analyzing data.

9.
Stat Methods Med Res ; 33(5): 838-857, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38549457

RESUMEN

Cluster randomization trials with survival endpoint are predominantly used in drug development and clinical care research when drug treatments or interventions are delivered at a group level. Unlike conventional cluster randomization design, stratified cluster randomization design is generally considered more effective in reducing the impacts of imbalanced baseline prognostic factors and varying cluster sizes between groups when these stratification factors are adopted in the design. Failure to account for stratification and cluster size variability may lead to underpowered analysis and inaccurate sample size estimation. Apart from the sample size estimation in unstratified cluster randomization trials, there are no development of an explicit sample size formula for survival endpoint when a stratified cluster randomization design is employed. In this article, we present a closed-form sample size formula based on the stratified cluster log-rank statistics for stratified cluster randomization trials with survival endpoint. It provides an integrated solution for sample size estimation that account for cluster size variation, baseline hazard heterogeneity, and the estimated intracluster correlation coefficient based on the preliminary data. Simulation studies show that the proposed formula provides the appropriate sample size for achieving the desired statistical power under various parameter configurations. A real example of a stratified cluster randomization trial in the population with stable coronary heart disease is presented to illustrate our method.


Asunto(s)
Ensayos Clínicos Controlados Aleatorios como Asunto , Tamaño de la Muestra , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Análisis por Conglomerados , Análisis de Supervivencia , Modelos Estadísticos
10.
Diabetes Metab ; 50(5): 101554, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38950854

RESUMEN

BACKGROUND: The association between dietary magnesium (Mg) intake and the risk of atherosclerotic cardiovascular disease (ASCVD) remains uncertain. We aimed to examine the associations of dietary Mg intake with the risk of ASCVD events and mortality in individuals with and without type 2 diabetes. METHODS: A total of 149,929 participants (4603 with type 2 diabetes) from the UK Biobank were included in the analyses. The hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models. Furthermore, interactions of dietary Mg intake with type 2 diabetes status were examined on multiplicative and additive scales. RESULTS: During a median follow-up of 12.0 and 12.1 years, 7811 incident ASCVD events and 5000 deaths (including 599 ASCVD deaths) were documented, respectively. There were significantly negative associations between sufficient dietary Mg intake (equal to or greater than the recommended daily intake) and the risk of ASCVD incidence (HR 0.63 [95 % CI 0.49;0.82]), ASCVD mortality (0.45 [0.24;0.87]), and all-cause mortality (0.71 [0.52;0.97]) in participants with type 2 diabetes, whereas no significant association was observed in participants without type 2 diabetes (1.01 [0.94;1.09] for ASCVD incidence; 1.25 [0.93;1.66] for ASCVD mortality; 0.97 [0.88;1.07] for all-cause mortality). Multiplicative and additive interactions of dietary Mg intake with type 2 diabetes status were both observed. CONCLUSION: Sufficient dietary Mg intake was significantly associated with lower risks of ASCVD events and mortality in individuals with type 2 diabetes but not in those without type 2 diabetes. Our findings provide insight into the importance of dietary Mg intake for reducing modifiable cardiovascular burden in individuals with type 2 diabetes, which may inform future personalized dietary guidelines.


Asunto(s)
Aterosclerosis , Bancos de Muestras Biológicas , Diabetes Mellitus Tipo 2 , Magnesio , Humanos , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Magnesio/administración & dosificación , Masculino , Persona de Mediana Edad , Reino Unido/epidemiología , Estudios Prospectivos , Aterosclerosis/epidemiología , Aterosclerosis/mortalidad , Anciano , Dieta , Adulto , Factores de Riesgo , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Biobanco del Reino Unido
11.
Oxid Med Cell Longev ; 2023: 4945288, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37082103

RESUMEN

Necroptosis is one of programmed cell death discovered recently, which involves in tumorigenesis, cancer metastasis, and immune reaction. We studied the necroptosis-related genes (NRGs) in ovarian cancer (OV) tissues using data from public databases, which separated into two NRGclusters. Patients in cluster A would have severe clinical characteristics, poor prognosis, and worse tumor microenvironment infiltration characteristics. The NRG score was achieved through the Cox analysis, along with a construction of a prognostic model. People with lower risk score would have better prognosis, lower expression of redox related genes, higher immunogenicity, and better effect on immunotherapy. In addition, the NRG score was closely related to cancer stem cell index, copy number variations, tumor mutation load, and chemosensitivity. We built a nomogram to enhance clinical application of the signature. These outcomes can help use know the function of NRGs in OV and provide new ideas for evaluating clinical outcome and developing more effective treatment protocols.


Asunto(s)
Variaciones en el Número de Copia de ADN , Neoplasias Ováricas , Humanos , Femenino , Necroptosis , Microambiente Tumoral , Neoplasias Ováricas/genética , Oxidación-Reducción
12.
Mol Ther Nucleic Acids ; 27: 1036-1055, 2022 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-35228898

RESUMEN

Uterine corpus endometrial carcinoma (UCEC) is a malignant disease globally, and there is no unified prognostic signature at present. In our study, two clusters were identified. Cluster 1 showed better prognosis and higher infiltration level, such as tumor microenvironment (TME), tumor mutation burden (TMB), and immune checkpoint genes expression. Gene set enrichment analysis (GSEA) indicated that some tumor-related pathways and immune-associated pathways were exposed. What is more, six pyroptosis-related long noncoding RNAs (lncRNAs) (PRLs) were applied to establish a prognostic signature through multiple Cox regression analysis. In both training and testing sets, patients with higher risk score had poorer survival than patients with low risk. The area under the curve (AUC) of receiver operating characteristic (ROC) curves performed that the survival probability was better in people with lower risk score. Mechanism analysis revealed that high risk score was correlated with reduced immune infiltration and T cells exhaustion, matching the definition of an "immune-desert" phenotype. Patients with lower risk score were characterized by higher immune checkpoint gene expression and TMB and have a sensitive response to immunotherapy and chemotherapy compared with patients with high risk score. The signature has accurate prediction ability of UCEC and is a promising therapeutic target to improve the effect of immunotherapy.

13.
Cancers (Basel) ; 14(16)2022 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-36011053

RESUMEN

Background: OV is the most lethal gynecological malignancy. M6A and lncRNAs have a great impact on OV development and patient immunotherapy response. In this paper, we decided to establish a reliable signature of mRLs. Method: The lncRNAs associated with m6A in OV were analyzed and obtained by co-expression analysis of the TCGA-OV database. Univariate, LASSO and multivariate Cox regression analyses were employed to establish the model of mRLs. K-M analysis, PCA, GSEA and nomogram based on the TCGA-OV and GEO database were conducted to prove the predictive value and independence of the model. The underlying relationship between the model and TME and cancer stemness properties were further investigated through immune feature comparison, consensus clustering analysis and pan-cancer analysis. Results: A prognostic signature comprising four mRLs, WAC-AS1, LINC00997, DNM3OS and FOXN3-AS1, was constructed and verified for OV according to the TCGA and GEO database. The expressions of the four mRLs were confirmed by qRT-PCR in clinical samples. Applying this signature, one can identify patients more effectively. The samples were divided into two clusters, and the clusters had different overall survival rates, clinical features and tumor microenvironments. Finally, pan-cancer analysis further demonstrated that the four mRLs were significantly related to immune infiltration, TME and cancer stemness properties in various cancer types. Conclusions: This study provided an accurate prognostic signature for patients with OV and elucidated the potential mechanism of the mRLs in immune modulation and treatment response, giving new insights into identifying new therapeutic targets.

14.
Comput Struct Biotechnol J ; 20: 5440-5452, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36249562

RESUMEN

Pyroptosis, a form of inflammatory programmed cell death, is accompanied by inflammation and participate in the body's immune response. The expression of pyroptosis-related genes (PRGs) is associated with tumor prognosis in ovarian cancer (OC), but it is still unknown whether pyroptosis can affect tumor immune microenvironment (TME) of OC. Based on 30 PRGs, we comprehensively assessed the pyroptosis patterns by using PRGscore and correlated them with TME features in 474 OC patients. Finally, we identified three pyroptosis modification patterns and TME immune characteristics of these patterns were in response to three immune phenotypes (immune-desert, immune-inflamed, and immune-excluded phenotypes). PRGscore can predict patient survival, staging, grading, and immunotherapy efficacy. Low PRGscore was associated with better survival advantage and increased mutation burden. Low PRGscore patients showed significantly better therapeutic effects and clinical results in chemotherapy and immunotherapy. Besides, the capability of PRGscore in predicting prognosis and immunotherapy sensitivity was further verified in other three tumor cohorts. In conclusion, the comprehensive assessment of OC pyroptosis modifications can help enhancing our understanding of TME immune infiltration and provide better personalized treatment tactics for OC patients.

15.
Oxid Med Cell Longev ; 2022: 2754836, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35965688

RESUMEN

Uterine corpus endometrial carcinoma (UCEC) is a malignant disease that, at present, has no well-characterised prognostic biomarker. In this study, two clusters were identified based on 28 N1-methyladenosine- (m1A-) related long noncoding RNAs (lncRNAs), of which cluster 1 was related to immune pathways according to the results of an enrichment analysis. We further observed better prognosis in patients with higher levels of immune cell infiltration, tumor mutation burden, microsatellite instability, and immune checkpoint gene expression. In addition, through Cox regression analysis and least absolute shrinkage and selection operator regression analysis, 10 m1A-related lncRNAs (mRLs) were employed to build a prognosis model. We found that people in higher risk categories had a poorer survival probability than those in lower risk. Low-risk samples were enriched with immune-related pathways, while the high-risk group was similar to the definition of the "immune desert" phenotype, which was associated with decreased immune infiltration, T cell failure, and decreased tumor mutation burden, while also being insensitive to immunotherapy and chemotherapy. This mRL-based model has the ability to accurately predict the prognosis of UCEC patients, and the mRLs could become promising therapeutic targets in enhancing the response of immunotherapy.


Asunto(s)
Neoplasias Endometriales , ARN Largo no Codificante , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunidad , ARN Largo no Codificante/genética
16.
Cancers (Basel) ; 14(14)2022 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-35884444

RESUMEN

Redox plays a central part in the pathogeneses and development of tumors. We comprehensively determined the expression patterns of redox-related genes (RRGs) in endometrial carcinoma (EC) cohorts from public databases and identified four different RRG-related clusters. The prognosis and the characteristics of TME cell infiltration of RRGcluster C patients were worse than those of other RRG clusters. When it comes to the gene cluster, there were great differences in clinicopathology traits and immunocyte infiltration. The RRG score was calculated by Cox analyses, and an RRG-based signature was developed. The risk score performed well in the EC cohort. Samples were separated into two risk subgroups with the standard of the value of the median risk score. Low-risk patients had a better prognosis and higher immunogenicity. In addition, RRG score was closely associated with immunophenoscore, microsatellite instability, tumor mutation burden, tumor stem cell index, copy number variation and chemotherapy sensitivity. The nomogram accurately predicted the prognosis of patients, and our model showed better performance than other published models. In conclusion, we built a prognostic model of RRGs which can help to evaluate clinical outcomes and guide more effective treatment.

17.
J Oncol ; 2022: 6951885, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36284631

RESUMEN

Background: Cervical cancer is the fourth common cancer among women. Its prognosis needs our more attention. Our purpose was to identity new prognostic gene sets to help other researchers develop more effective treatment for cervical cancer patients and improve the prognosis of patients. Methods: We used gene set variation analysis (GSVA) to calculate the enrichment scores of gene sets and identified three subtypes of cervical cancer through the Cox regression model, k-means clustering algorithm, and nonnegative matrix factorization method (NMF). Chi-square test was utilized to test whether a certain clinical characteristic is different among divided subtypes. We further screened the prognostic gene sets using differential analysis, univariate Cox regression analysis, and least absolute shrinkage and selection operator (LASSO) regression. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to analyze which pathways and function the genes from screened gene sets enriched. Search Tool for the Retrieval of Interacting Genes (STRING) was used to draw the protein-protein interaction network, and Cytoscape was used to visualize the hub genes of protein-protein interaction network. Results: We identified three novel subtypes of cervical cancer in The Cancer Genome Atlas (TCGA) samples and validated in Gene Expression Omnibus (GEO) samples. There were significant variations between the three subtypes in histological type, T stage, M stage, and N stage. T_GSE36888_UNTREATED_VS_IL2_TREATED_STAT5_AB_KNOCKIN_TCELL_2H_UP and N_HALLMARK_ANGIOGENESIS were screened prognostic gene sets. The prognostic model was as follows: riskScore = T_GSE36888_UNTREATED_VS_IL2_TREATED_STAT5_AB_KNOCKIN_TCELL_2H_UP∗ 2.617 + N_HALLMARK_ANGIOGENESIS∗ 4.860. Survival analysis presented that in these two gene sets, high enrichment scores were all significantly related to worse overall survival. The hub genes from T gene set included CXCL1, CXCL2, CXCL8, ALDOA, TALDO1, LDHA, CCL4, FCAR, FCER1G, SAMSN1, LILRB1, SH3PXD2B, PPM1N, PKM, and FKBP4. As for N gene sets, the hub genes included ITGAV, PTK2, SPP1, THBD, and APOH. Conclusions: Three novel subtypes and two prognostic gene sets were identified. 15 hub genes for T gene set and 5 hub genes for N gene set were discovered. Based on these findings, we can develop more and more effective treatments for cervical cancer patients. Based on the gene enriched pathways, we can development specific drugs targeting the pathways.

18.
J Oncol ; 2022: 3477148, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35069733

RESUMEN

BACKGROUND: Serine/arginine-rich splicing factor 9 (SRSF9) is one of the members of SRSF gene family and related to the tumorigenesis and the progression of tumor. However, whether SRSF9 has a crucial role across pan-cancer is still unknown. METHODS: In this study, we used public databases, such as The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx), to analyze SRSF9 expression level among tumor and normal cells. Survival analysis, K-M plotter, and PrognoScan were used to analyze the prognosis value of SRSF9, regarding to overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Moreover, we performed the correlation between SRSF9 and clinical characteristics (including the outcome of prognosis), as well as molecular events of tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoint gene, tumor microenvironment (TME), immune infiltrating cells, mismatch repair (MMR) genes, m6A genes, DNA methyltransferases, and neoantigen with bioinformatics methods and TISIDB, TIMER, and Sangerbox websites. RESULTS: In general, SRSF9 expression was upregulated in most cancers, such as BLCA, CHOL, and UCEC, which SRSF9 was associated with short survival and severe progression. In COAD, STAD, and UCEC, SRSF9 expression was positively related to both TMB and MSI. In BRCA, BLCA, ESCA, GBM, HNSC, LUSC, LUAD, OV, PRAD, TGCT, THCA, and UCEC, both immune score and stomal score showed a negative relationship with SRSF9 expression. Immune score showed a positive relationship with SRSF9 expression in LGG. SRSF9 expression had a significant and positive correlation with six types of immune infiltration cells in LGG, KIRC, LIHC, PCPG, PRAD, SKCM, THCA, and THYM, except in LUSC. In LIHC, SRSF9 was highly significant correlated with most immune checkpoint genes. For neoantigens, correlation between SRSF9 and the quantity of neoantigens was significantly positive in some cancer types. SRSF9 was also correlated with MMR genes, m6A genes, and DNA methyltransferases. In the 33 cancer types, gene set enrichment analysis (GSEA) demonstrated that SRSF9 was correlated with multiple functions and signaling pathways. CONCLUSION: These findings demonstrated that SRSF9 may be a new biomarker for the prognosis and immunotherapy in various cancers. As a result, it will be beneficial to provide new therapies for cancer patients, thereby improving the treatment and prognosis of cancer patients.

19.
Hypertens Res ; 45(3): 516-526, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35031774

RESUMEN

This study aimed to evaluate the association between dietary polyunsaturated fatty acid (PUFA) intake and the prevalence of hypertension in U.S. adults. Data from the National Health and Nutrition Examination Survey (NHANES) 2009-2016 were used. Total PUFAs and subtypes of PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), linoleic acid (LA), and arachidonic acid (AA), were obtained through two 24 h recalls and adjusted by body weight. Hypertension was defined as the average of three measurements of blood pressure above 130/80 mmHg or taking antihypertensive medication. Weighted odds ratios (ORs) of hypertension and adjusted rate differences (ARDs) in prevalence, as well as their 95% confidence intervals (CIs), were estimated by using the logistic regression model of survey design. A total of 17,108 participants were included in this study. Dietary intake of PUFAs was significantly associated with a lower prevalence of hypertension for the highest versus lowest quartiles. The weighted ORs with 95% CIs of hypertension for total PUFA, omega-3 fatty acid, fish oil, ALA, omega-6 fatty acid, LA and AA were 0.47(0.40-0.55), 0.61(0.51-0.72), 0.85(0.74-0.97), 0.65(0.55-0.76), 0.49(0.42-0.58), 0.49(0.42-0.57) and 0.75(0.64-0.89), and the ARDs with 95% CIs were -18.06%(-22.54%, -13.58%), -12.06%(-16.68%, -7.44%), -4.13%(-8.25%, -0.01%), -10.54%(-15.31%, -5.78%), -17.03%(-21.49%, -12.58%), -17.23%(-21.76%, -12.69%) and -6.91%(-11.37%, -2.46%), respectively. Our study proposed that the intake of total PUFAs, omega-3 fatty acids, fish oil, ALA, omega-6 fatty acids, LA, and AA was associated with a lower prevalence of hypertension in the U.S. adults.


Asunto(s)
Ácidos Grasos Omega-3 , Hipertensión , Estudios Transversales , Ingestión de Alimentos , Ácido Eicosapentaenoico , Ácidos Grasos Insaturados , Humanos , Hipertensión/epidemiología , Encuestas Nutricionales , Prevalencia
20.
Front Cell Dev Biol ; 9: 753004, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34901000

RESUMEN

Background: As the fourth most common malignant tumors in women, uterine corpus endometrial carcinoma (UCEC) requires novel and reliable biomarkers for prognosis prediction to improve the overall survival. Oxidative phosphorylation (OXPHOS) is found to be strongly correlated with the progression of tumor. Here, we aimed to construct an OXPHOS-related and immune microenvironment prognostic signature to stratify UCEC patients for optimization of treatment strategies. Method: Prognosis-associated OXPHOS-related differentially expressed genes were identified by multivariable Cox regression from TCGA-UCEC cohort. Based on the candidate genes, an OXPHOS-related prognostic signature was constructed by the train set data and verified by the entire set. When integrated with relevant clinical characteristics, a nomogram was also created for clinical application. Through comparison of tumor microenvironment between different risk groups, the underlying mechanism of the model and the inner correlation between immune microenvironment and energy metabolism were further investigated. Results: An OXPHOS-related signature containing ATP5IF1, COX6B1, FOXP3, and NDUFB11 was constructed and had better predictive ability compared with other recently published signatures in UCEC. Patients with lower risk score showed higher immune cell infiltration, higher ESTIMATE score (p = 2.808E-18), lower tumor purity (p = 2.808E-18), higher immunophenoscores (IPSs) (p < 0.05), lower expression of mismatch repair (MMR) proteins (p < 0.05), higher microsatellite instability (MSI), lower expression of markers of N6-methyladenosine (m6A) mRNA methylation regulators, higher tumor mutation burden (TMB) (p = 1.278E-9), and more sensitivity to immune checkpoint blockade (ICB) (p < 0.001) and chemotherapy drugs, thus, possessing improved prognosis. Conclusion: An OXPHOS-related and immune microenvironment prognostic signature classifying EC patients into different risk subsets was constructed in our study, which could be used to predict the prognosis of patients and help to select a specific subset of patients who might benefit from immunotherapy and chemotherapy, thus, improving the overall survival rate of UCEC. These findings may contribute to the discovery of novel and robust biomarkers or target therapy in UCEC and give new insights into the molecular mechanism of tumorigenesis and progression of UCEC.

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